22-24302061-T-A

Variant names:

• chr22-24302061-T-A
• rs545888691
• NM_015330.6:c.-37-134T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015330.6(SPECC1L):​c.-37-134T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 614,716 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (142 hom., cov: 32)
  • Exomes 𝑓: 0.015 (31 hom.)
• Consequence: SPECC1L NM_015330.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.460
• Publications: 0 publications found

Genes affected

SPECC1L (HGNC:29022): (sperm antigen with calponin homology and coiled-coil domains 1 like) This gene encodes a coiled-coil domain containing protein. The encoded protein may play a critical role in actin-cytoskeletal reorganization during facial morphogenesis. Mutations in this gene are a cause of oblique facial clefting-1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A read-through transcript composed of SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and the downstream ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding. [provided by RefSeq, Jun 2013]

SPECC1L-ADORA2A (HGNC:49185): (SPECC1L-ADORA2A readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) genes on chromosome 22. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-24302061-T-A is Benign according to our data. Variant chr22-24302061-T-A is described in ClinVar as Benign. ClinVar VariationId is 1239666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015330.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L	NM_015330.6	MANE Select	c.-37-134T>A		intron	N/A	NP_056145.5	Q69YQ0-1
	SPECC1L	NM_001145468.4		c.-37-134T>A		intron	N/A	NP_001138940.4	Q69YQ0-1
	SPECC1L	NM_001254732.3		c.-37-134T>A		intron	N/A	NP_001241661.3	Q69YQ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L	ENST00000314328.14	TSL:1 MANE Select	c.-37-134T>A		intron	N/A	ENSP00000325785.8	Q69YQ0-1
	SPECC1L	ENST00000437398.5	TSL:1	c.-37-134T>A		intron	N/A	ENSP00000393363.1	Q69YQ0-1
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.-37-134T>A		intron	N/A	ENSP00000351480.2	F8WAN1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4722 AN: 150448 Hom.: 140 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.00233

Gnomad SAS AF: 0.00590

Gnomad FIN AF: 0.00809

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0252

GnomAD4 exome AF: 0.0148 AC: 6848 AN: 464150 Hom.: 31 AF XY: 0.0141 AC XY: 3460 AN XY: 245874

African (AFR) AF: 0.0738 AC: 843 AN: 11430

American (AMR) AF: 0.0198 AC: 330 AN: 16658

Ashkenazi Jewish (ASJ) AF: 0.0318 AC: 415 AN: 13048

East Asian (EAS) AF: 0.00442 AC: 107 AN: 24206

South Asian (SAS) AF: 0.00671 AC: 314 AN: 46820

European-Finnish (FIN) AF: 0.00685 AC: 215 AN: 31396

Middle Eastern (MID) AF: 0.0146 AC: 27 AN: 1848

European-Non Finnish (NFE) AF: 0.0141 AC: 4160 AN: 294920

Other (OTH) AF: 0.0183 AC: 437 AN: 23824

GnomAD4 genome AF: 0.0315 AC: 4748 AN: 150566 Hom.: 142 Cov.: 32 AF XY: 0.0308 AC XY: 2267 AN XY: 73560

African (AFR) AF: 0.0750 AC: 3057 AN: 40764

American (AMR) AF: 0.0280 AC: 424 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 100 AN: 3456

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5140

South Asian (SAS) AF: 0.00590 AC: 28 AN: 4746

European-Finnish (FIN) AF: 0.00809 AC: 84 AN: 10386

Middle Eastern (MID) AF: 0.0245 AC: 7 AN: 286

European-Non Finnish (NFE) AF: 0.0145 AC: 980 AN: 67676

Other (OTH) AF: 0.0269 AC: 56 AN: 2084

Alfa AF: 0.0234 Hom.: 12

Bravo AF: 0.0338

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.11
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs545888691; hg19: chr22-24698029;